Synthesis and evaluation of non-dimeric HCV NS5A inhibitors

Bioorg Med Chem Lett. 2013 Apr 1;23(7):2031-4. doi: 10.1016/j.bmcl.2013.02.023. Epub 2013 Feb 13.

Abstract

Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Carbamates
  • Cell Line
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Hepacivirus / drug effects
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrrolidines
  • Structure-Activity Relationship
  • Valine / analogs & derivatives
  • Vero Cells
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir